Lec 7: Inflammation Flashcards
What is the main function of inflammation?
- remove infection or damaged tissue to restore homeostasis
- crucial to maintaining the health and integrity of an organism
- soluble mediators and cellular components work together in a systemic fashion
What 2 responses is inflammation divided into?
acute and chronic
What are the 4 physiological changes that accompany acute inflammation?
- vasodilation
- permeability
- recruitment of leukocytes
- fever
What are the 4 clinical signs that accompany acute inflammation?
- rubor (redness)
- dolor (pain)
- calor (heat)
- tumor (swelling)
Describe vasodilation
- one of the earliest physical responses to acute tissue injury
- arterioles are the first to be involved, followed by the capillary beds, resulting in a net increase in blood flow
- increased blood flow results in the characteristic heat and redness associated with foci of acute inflammation
Describe vascular permeability
- under normal conditions, vascular endothelial cells function as a semi-permeable membrane, restricting the plasma proteins to the intravascular space
- in response to inflammatory stimuli, endothelial cells lining the venues contract, widening the intercellular junctions to produce gaps, permitting passage of plasma proteins and facilitating leukocyte extravasation.
- more severe injury is associated with endothelial cell necrosis
Describe leukocyte recruitment
- process recruits leukocytes from bloodstream and ultimately involves the bone marrow to focus on inflammatory activity
- these leukocytes migrate through the enlarged endothelial cell junctions and the basement membrane
Describe fever.
- agents producing fever (pyrogens) are released from leukocytes in response to specific stimuli, such as bacterial endotoxin
- a number of soluble pro inflammatory mediators have been implicated in this process (IL1, TNFa) and prostaglandins
- possible beneficial role of fever with respect to lymphocyte trafficking
Describe what can be seen with inflammation at the microscopic scale?
- dilated post capillary venules
- leukocytes marginating on epithelia
- mild expansion of superficial dermis
- edema
How is inflammation initiated?
- innate immune recognition triggers an inflammatory response that focuses the immune system on the site of infection
- inflammation requires the coordinated response from blood vessels and leukocytes
Describe the 3 things that can trigger inflammation.
- pathogens: activation of the plasma protease systems by interaction with degradation products of the bacterial cell walls; secretion of toxins
- injured cells: release degradation products that initiate one or more of the plasma protease cascades; up regulate expression of soluble molecules (pro inflammatory cytokines)
- foreign bodies from exogenous or endogenous sources, physical injury, chemical agents
Describe how TLRs initiate pro inflammatory responses.
- first line of defence against incoming pathogens
- well conserved across evolution
- remember that they work together with several other types of recognition receptors (e.g. resident macrophages, epithelial cells)
Describe the TLR signalling pathway.
TLRS - MyD88 dependent or indepndent pathways - transcription factors - gene expression - functional protein - cellular response
Why do TLRs share many cellular responses?
- share MyD88 and NfKb
What are the 3 types of inflammatory mediators?
- cytokines
- chemokines
- hormones